Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation

Human embryonic stem cells (hESCs) demonstrate remarkable proliferative and developmental capacity. Clinical interest arises from their ability to provide an apparently unlimited cell supply for transplantation, and from the hope that they can be directed to desirable phenotypes in high purity. Here...

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Bibliographic Details
Published in:Glia 2005-02, Vol.49 (3), p.385-396
Main Authors: Nistor, Gabriel I., Totoiu, Minodora O., Haque, Nadia, Carpenter, Melissa K., Keirstead, Hans S.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Differentiation - physiology
Cell Line
Demyelinating Diseases - embryology
Demyelinating Diseases - pathology
Demyelinating Diseases - surgery
differentiation
Embryo, Mammalian
Fundamental and applied biological sciences. Psychology
human embryonic stem cells
Humans
Isolated neuron and nerve. Neuroglia
Mice
Mice, Neurologic Mutants
Myelin Sheath - physiology
Myelin Sheath - transplantation
oligodendrocyte
Oligodendroglia - cytology
Oligodendroglia - transplantation
progenitor
remyelination
Spinal Cord - cytology
Spinal Cord - embryology
Spinal Cord - transplantation
Stem Cell Transplantation - methods
transplantation
Vertebrates: nervous system and sense organs
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Summary:Human embryonic stem cells (hESCs) demonstrate remarkable proliferative and developmental capacity. Clinical interest arises from their ability to provide an apparently unlimited cell supply for transplantation, and from the hope that they can be directed to desirable phenotypes in high purity. Here we present for the first time a method for obtaining oligodendrocytes and their progenitors in high yield from hESCs. We expanded hESCs, promoted their differentiation into oligodendroglial progenitors, amplified those progenitors, and then promoted oligodendroglial differentiation using positive selection and mechanical enrichment. Transplantation into the shiverer model of dysmyelination resulted in integration, differentiation into oligodendrocytes, and compact myelin formation, demonstrating that these cells display a functional phenotype. This differentiation protocol provides a means of generating human oligodendroglial lineage cells in high purity, for use in studies of lineage development, screening assays of oligodendroglial‐specific compounds, and treating neurodegenerative diseases and traumatic injuries to the adult CNS. © 2004 Wiley‐Liss, Inc.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.20127